The epidermis of human skin is a constantly regenerating tissue which gives rise to a number of pathologic conditions characterized by altered rates of cellular proliferation. Cell population kinetics have been extensively investigated in animals. Very few such studies have been performed on humans because of limitations in tissue sampling and the large systemic doses of radioactivity that are required. The proposed investigation takes advantage of the easy accessibility of skin to study human cell proliferation and the biochemistry of DNA synthesis in a spectrum of proliferative cutaneous diseases that include psoriasis, ichthyosis, primary skin cancers, and the cutaneous metastasis of internal malignancies. Information to be obtained on the phases of the cell cycle, e.g., the G1 interphase, the DNA synthesis period, the G2 rest period, and the mitotic period, is of critical importance in understanding the mechanisms of normal and abnormal cell reproduction. Biochemical and autoradiographic technics will be used to find and evaluate metabolic steps that are or would be susceptible to chemotherapeutic drugs in the treatment of proliferative diseases. Studies using chemotherapeutic drugs such as methotrexate will be performed in vitro and in vivo to determine their mechanism of action and better ways to use these drugs.